Project Description The main focus of this application is on the functions of G-proteins in endothelial cells. G-protein G?13 is critical for blood vessel formation. This proposal builds on our discovery of a novel mechanism by which G?13 functions through SOS, a direct regulator of Ras and the new observation that endothelial cell-specific deletion of G?13 impairs organ regeneration. The first aim is to dissect the biochemical mechanism by which G?13 regulates SOS in vitro. The second aim is to determine how G?13 and G-protein- coupled receptors regulate SOS in cells. The third aim is to investigate the impact of endothelial cell-specific deletion of SOS1 on organ regeneration.